Lynch-like Syndrome: Potential Mechanisms and Management

Alejandro Martínez-Roca; Mar Giner-Calabuig; Oscar Murcia; Adela Castillejo; José Luis Soto; Anabel García-Heredia; Rodrigo Jover

doi:10.3390/cancers14051115

Lynch-like Syndrome: Potential Mechanisms and Management

Alejandro Martínez-Roca, Mar Giner-Calabuig, Oscar Murcia, Adela Castillejo, José Luis Soto, Anabel García-Heredia, Rodrigo Jover

Research output: Contribution to journal › Review article › peer-review

6 Scopus citations

Abstract

Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adequate classification of these patients is still lacking. For this reason, management of Lynch-like syndrome and prevention of cancer in these families is clinically challenging. This review explains the concept of Lynch-like syndrome, potential mechanisms for its development, and methods for adequately distinguishing between sporadic and hereditary cases of this entity.

Original language	English
Article number	1115
Journal	Cancers
Volume	14
Issue number	5
DOIs	https://doi.org/10.3390/cancers14051115
State	Published - 1 Mar 2022

Bibliographical note

Funding Information:
This work was supported by the Instituto de Salud Carlos III (PI17/01756 and PI20/01527). Asociación Española de Gastroenterología Grants (Tamarite 2015 “Caracterización molecular del síndrome de Lynch-Like”). Fundación Instituto de Investigación Sanitaria y Biomédica de Alicante ISABIAL (UGP-21-172—UGP-20-207 and UGP-21-104). Alejandro Martínez-Roca and Oscar Murcia received PFIS grant from the Instituto de Salud Carlos III (FI18/00301-CM18/00058). Anabel GarcíaHeredia received a Sara Borrell grant from the Instituto de Salud Carlos III (CD19/00133). Asociación para la Investigación en Gastroenterología de la Provincia de Alicante (AIGPA), a private association that promotes research in gastrointestinal diseases in Alicante, also supported the logistical aspects of the study, but declares no conflict of interest.

Funding Information:
Funding: This work was supported by the Instituto de Salud Carlos III (PI17/01756 and PI20/01527). Asociación Española de Gastroenterología Grants (Tamarite 2015 “Caracterización molecular del síndrome de Lynch-Like”). Fundación Instituto de Investigación Sanitaria y Biomédica de Alicante ISABIAL (UGP-21-172—UGP-20-207 and UGP-21-104). Alejandro Martínez-Roca and Oscar Murcia received PFIS grant from the Instituto de Salud Carlos III (FI18/00301-CM18/00058). Anabel García-Heredia received a Sara Borrell grant from the Instituto de Salud Carlos III (CD19/00133). Asociación para la Investigación en Gastroenterología de la Provincia de Alicante (AIGPA), a private association that promotes research in gastrointestinal diseases in Alicante, also supported the logistical aspects of the study, but declares no conflict of interest.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Colorectal cancer
DNA mismatch repair genes
Hereditary cancer
Lynch syndrome
Lynch-like syndrome

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title = "Lynch-like Syndrome: Potential Mechanisms and Management",

abstract = "Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adequate classification of these patients is still lacking. For this reason, management of Lynch-like syndrome and prevention of cancer in these families is clinically challenging. This review explains the concept of Lynch-like syndrome, potential mechanisms for its development, and methods for adequately distinguishing between sporadic and hereditary cases of this entity.",

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AU - García-Heredia, Anabel

AU - Jover, Rodrigo

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N2 - Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adequate classification of these patients is still lacking. For this reason, management of Lynch-like syndrome and prevention of cancer in these families is clinically challenging. This review explains the concept of Lynch-like syndrome, potential mechanisms for its development, and methods for adequately distinguishing between sporadic and hereditary cases of this entity.

AB - Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adequate classification of these patients is still lacking. For this reason, management of Lynch-like syndrome and prevention of cancer in these families is clinically challenging. This review explains the concept of Lynch-like syndrome, potential mechanisms for its development, and methods for adequately distinguishing between sporadic and hereditary cases of this entity.

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Lynch-like Syndrome: Potential Mechanisms and Management

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Keywords

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